Amoeboid cells undergo durotaxis with soft end polarized NMIIA

Area of Science:

• Cellular Mechanobiology
• Immunology
• Developmental Biology

Background:

• Durotaxis, cell migration towards stiffer substrates, is crucial in development, wound healing, and cancer.
• Mesenchymal cell durotaxis mechanisms are known, but immune cell amoeboid migration in response to mechanical cues is poorly understood.
• Immune cells play complex roles alongside non-immune cells in various physiological and pathological processes.

Purpose of the Study:

• To investigate whether immune cells migrating in an amoeboid mode exhibit durotaxis.
• To elucidate the underlying molecular mechanisms of amoeboid durotaxis in immune cells.
• To explore the evolutionary conservation and theoretical modeling of amoeboid durotaxis.

Main Methods:

• Development of an imaging-based confined migration device with a controlled stiffness gradient.
• Live cell trajectory tracking and directional analysis of T cells and neutrophils.
• Utilized the protist *Dictyostelium* to study evolutionary conservation and employed an active gel model for theoretical analysis.

Main Results:

• Observed that amoeboid cells, including T cells and neutrophils, exhibit durotaxis, migrating towards softer substrates.
• Identified non-muscle myosin IIA (NMIIA) polarization towards the softer matrix as a key mechanism, independent of differential actin flow.
• Demonstrated evolutionary conservation of amoeboid durotaxis in *Dictyostelium* and successfully modeled the phenomena using an active gel theory.

Conclusions:

• Amoeboid cells possess the capability for durotaxis, challenging previous assumptions based on mesenchymal migration.
• NMIIA polarization is a critical factor in immune cell durotaxis, offering insights into cell migration in heterogeneous environments.
• Findings have implications for understanding immune surveillance, cancer cell migration in tumors, and cell behavior in fibrotic tissues.